Introduction: In most forms of dystonia there is uncertainty about brain regions primary involved, which are therefore thought to have functional rather than structural abnormalities. We report that changes of phosphodiesterase-10A (PDE10A) immunoreactivity map the involvement of the basal ganglia in TorsinA DYT1 knock-in mice, a transgenic model of the most common primary dystonia. PDE10A, a key enzyme in the catabolism of cAMP and cGMP, has unique distribution in the basal ganglia, within medium spiny neurons in the striatum, and in their axons/terminals in the substantia nigra pars reticulata and external globus pallidus. Material and methods: PDE10A was studied in control mice and in mice carrying either human wild-type torsinA or mutant torsinA. Rabbit anti-PDE10A was used for immunohistochemical identification of PDE10A neurons and nerve fibers. Quantitative analysis of PDE10A expressions in the different brain areas was assessed by Western blotting. Results: In control mice prominent PDE10A-like immunoreactivity was observed in neuronal bodies and in the neuropil throughout the caudate-putamen; moreover intense PDE10A-likeimmunoreactivity was observed in neuropil and nerve fibers of the globus pallidus, and substantia nigra pars reticulata. Biochemical and morphological studies demonstrate that PDE10A expression was clearly increased in the globus pallidus of mice carrying DYT1TorsinA mutation, while in substantia nigra the PDE10A immunoreactivity was overexpressed both in mice carrying wild-type human TorsinA and in mice carrying DYT1 TorsinA mutation. Conclusions: Our study demonstrates that PDE10A may act as translational biomarker in the external globus pallidus of animals with dystonia, which could be investigated in vivo by novel PDE10A PET ligands.

Hyper-expression of phosphodiesterase-10A in striato-nigral and striato-pallidal pathways of Torsin-A knock-in mice / Giorgi, Mauro; V., D'Angelo; V., Castelli; F., Palumbo; A., Martorana; G., Sancesario. - In: CLINICAL NEUROPATHOLOGY. - ISSN 0722-5091. - STAMPA. - 32:(2013), pp. 227-227. ((Intervento presentato al convegno Congresso dell'associazione italiana di neuropatologia e neurobiologia clinica tenutosi a Pisa nel 30 maggio- 1 giugno.

Hyper-expression of phosphodiesterase-10A in striato-nigral and striato-pallidal pathways of Torsin-A knock-in mice

GIORGI, MAURO;
2013

Abstract

Introduction: In most forms of dystonia there is uncertainty about brain regions primary involved, which are therefore thought to have functional rather than structural abnormalities. We report that changes of phosphodiesterase-10A (PDE10A) immunoreactivity map the involvement of the basal ganglia in TorsinA DYT1 knock-in mice, a transgenic model of the most common primary dystonia. PDE10A, a key enzyme in the catabolism of cAMP and cGMP, has unique distribution in the basal ganglia, within medium spiny neurons in the striatum, and in their axons/terminals in the substantia nigra pars reticulata and external globus pallidus. Material and methods: PDE10A was studied in control mice and in mice carrying either human wild-type torsinA or mutant torsinA. Rabbit anti-PDE10A was used for immunohistochemical identification of PDE10A neurons and nerve fibers. Quantitative analysis of PDE10A expressions in the different brain areas was assessed by Western blotting. Results: In control mice prominent PDE10A-like immunoreactivity was observed in neuronal bodies and in the neuropil throughout the caudate-putamen; moreover intense PDE10A-likeimmunoreactivity was observed in neuropil and nerve fibers of the globus pallidus, and substantia nigra pars reticulata. Biochemical and morphological studies demonstrate that PDE10A expression was clearly increased in the globus pallidus of mice carrying DYT1TorsinA mutation, while in substantia nigra the PDE10A immunoreactivity was overexpressed both in mice carrying wild-type human TorsinA and in mice carrying DYT1 TorsinA mutation. Conclusions: Our study demonstrates that PDE10A may act as translational biomarker in the external globus pallidus of animals with dystonia, which could be investigated in vivo by novel PDE10A PET ligands.
Congresso dell'associazione italiana di neuropatologia e neurobiologia clinica
04 Pubblicazione in atti di convegno::04d Abstract in atti di convegno
Hyper-expression of phosphodiesterase-10A in striato-nigral and striato-pallidal pathways of Torsin-A knock-in mice / Giorgi, Mauro; V., D'Angelo; V., Castelli; F., Palumbo; A., Martorana; G., Sancesario. - In: CLINICAL NEUROPATHOLOGY. - ISSN 0722-5091. - STAMPA. - 32:(2013), pp. 227-227. ((Intervento presentato al convegno Congresso dell'associazione italiana di neuropatologia e neurobiologia clinica tenutosi a Pisa nel 30 maggio- 1 giugno.
File allegati a questo prodotto
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/763471
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact